Chapter 15: The Chromosomal Basis of Inheritance
I. Relating Mendelism to chromosomes
-Improved microscopy techniques
-Cytologists worked out
-1875: Mitosis
-1890s: Meiosis
-1900: Cytology and genetics converged
-Parallels between behavior of chromosomes and behavior of Mendel’s factors
A. Chromosome theory of inheritance:
1. Mendelian genes have specific loci on chromosomes
2. Chromosomes undergo segregation and independent assortment
B. Morgan traced a gene to a specific chromosome
1. Drosophila melonogaster
a. Excellent choice of organism for genetic studies
1. Single mating produces: hundreds of offspring
2. New generations can breed every two weeks
3. 4 pairs of chromosomes that are easily distinguishable under the
microscope
B. Bred flies for a year
a. Wild Type: Phenotype most common in natural populations (red eyes)
b. Mutant Phenotypes: Traits that are alternatives to the wild type (White
eyes)
II. Discovery of sex linkage
A. Morgan mated white eyed male with red eyed female
1. F1: All red----> Wild dominant
2. F2: 3:1 phenotypic ratio
a. White eyes showed up only in males
b. All of the females had red eyes
c. 1/2 of the males had red eyes
d. 1/2 of the males had white eyes
3. Gene for eye color was located on the x chromosome
4. No corresponding eye-color locus on the y chromosome
a. Females (XX) carry 2 copies of the gene for this character
b. Will only have white eyes if she receives that allele on both X
chromosomes
c. Males (XY) carry only one
1. Needs only a single copy of the mutant allele to have white eyes
B. Sexlinked genes: Genes located on a sex chromosome
C. Linked Genes: Genes located on the same chromosome that tend to be inherited
together in genetic crosses
1. Passed along as a unit
2. Results from crosses deviate from Mendelian principle of independent
assortment
3. Experiment that involves body color and wing size
D. Genetic Recombination: Production of offspring with new combinations of traits
1. Recombination of unlinked genes: Independent assortment of chromosomes
a. Punnet square: Heterozygous yellow-round x green wrinkled
1. ½ matches one of parents phenotypes
2. Parental types: Test cross offspring whose phenotype is the same as the
P1 phenotypes (grandparents)
a. Recombinants: Offspring having different combinations of traits than
their
parents
1.Half of the offspring are recombinants: 50% frequency of
recombination
2. Random alignment of homologous chromosomes during
metaphase I
E. Recombination of Linked Genes: Crossing Over
1. Linked genes do not assort independently
a. Located on the same chromosome
b. Move together through meiosis
F. Test cross for body color and wing shape did not produce the expected 1:1:1:1 ratio
1. Lets do this cross
2. Morgan proposed that an exchange of segments between homologous
chromosomes
fragments
3.Crossover between chromatids of homologous chromosomes breaks linkages
that may bring together alleles in new combinations
II. Geneticists can use recombination data to map a chromosome’s genetic loci
A. 1917: Led Alfred H Sturtevant (one of Morgan’s students) to a method for
constructing genetic maps
1. Genetic map: An ordered list of the genetic loci along a particular
chromosome
a. Hypothesized recombination frequencies reflect different distances
between genes on a chromosome
1. Far apart: Higher probability for crossover event
2. Close together: Lower probability of being separated by a
crossover event
b. Used recombination data from fruit fly crosses to assign to genes
relative positions on chromosomes
2. Linkage map: Genetic map based on recombination frequencies
a. Map units: Distances between genes; one map unit is equivalent to a
1% recombination frequency
1. Modern: Centimorgan
3. Cytological maps: Maps of chromosomes that actually pinpoints genes
III. Sex Chromosomes and Sex-Linked Inheritance:
A. XX: Female
B. XY: Male
C. Meiosis occurs in testes or ovaries
1. X and Y chromosomes behave like homologous chromosomes
2. Undergo little crossing over with each other
D. Anatomical evidence of sex begins to emerge when the human embryo is about 2
months old
1. 1990 British research team identified a gene required for the development of
testes
a. Small region of the Y chromosome that confers masculinity
b.SRY: Sex determining region of Y chromosome
1. In it’s absence gonads develop into ovaries
2. Presence or absence of SRY is a trigger
a. Codes for a protein that regulates many other genes that
are involved in the biochemical, physiological and anatomical
features of sex determination
E. XY mechanism is only one of several
1. Bees and ants lack special sex chromosomes
a. Fertilized eggs develop into females (diploid)
b. Males develop from unfertilized eggs (haploid)
IV. Sex-Linked Disorders in Humans
A. In humans, Sex-linked usually refers to genes on the X chromosome
1. Traits follow the same pattern of inheritance for white eye locus in Drosophila
a. Fathers pass X-linked alleles to all their daughters and none to their sons
b. Mothers can pass sex-linked alleles to both sons and daughters
2. Recessive allele: Female will express the phenotype only if she is a
homozygote
3.Because males have only one locus: Homozygous and heterozygous lack
meaning
a. Hemizygous
b. Any male receiving the recessive allele from his mother will express the
trait
1. Sex linked recessive disorders are expressed more frequently in
males
B. Colorblindness
1. Example
C. Duchenne’s muscular dystrophy: Progressive weakening of the muscles and loss of
coordination
1. 1/3500 males in US
2. Rarely live past early 20s
3. Absence of key muscle protein: Dystrophin
D. Hemophilia: Sex-linked recessive trait defined by the absence of one or more of the
proteins required for blood clotting
1. Bleeding is prolonged: Firm clot is slow to form
2.Bleeding in muscles or joints (Occurs without known cause)
3. Today: Treated as needed with intravenous injections of missing protein
a. Ancient Hebrews had some understanding of the hereditary pattern
1. Sons born to women having a family history of hemophilia
2. Exempt from circumcision
4. High frequency has plagued royal families of Europe
a. First of royal line was Leopold, son of Queen Victoria (1819-1901) of
England
V. X-Inactivation in Females
A. One X chromosome in each cell becomes almost completely inactivated during
embryonic development
1. Barr body: Compact object formed from condensing inactive X chromosome
a. Lies along the inside of nuclear envelope
b. Most of the genes of the X chromosome that forms the Barr body are
not expressed
c. Reactivated in ovary cells that undergo meiosis to form eggs
2. Mary Lyon (British geneticist)
1. During early embryonic development
2. One or the other X is randomly inactivated in each cell
3. As embryonic cells divide by mitosis
a. Each gives rise to a population of cells having a specific X
chromosome active and the other inactive
b. Ex: Calico cat: Duel cell populations
1. Mosaicism
4. Humans; Recessive sex linked mutation that prevents development of sweat
glands
a. Heterozygous female
1. Patches of normal skin
2. Patches of skin lacking sweat glands
5. Inactivation of an X chromosome
1. Attachment of methyl groups (-CH3) to cytosine (DNA)
a. Which does it attach to?
b. XIST: X-inactive specific transcript
1. Gene found only on the Barr-body chromosome
c. Gene’s product: RNA molecule
1. Multiple copies attach to X chromosome where they are
made
2. Cover it
3. Initiates inactivation